US5817827A - Method for the dehydration of amides to nitriles - Google Patents
Method for the dehydration of amides to nitriles Download PDFInfo
- Publication number
- US5817827A US5817827A US08/734,987 US73498796A US5817827A US 5817827 A US5817827 A US 5817827A US 73498796 A US73498796 A US 73498796A US 5817827 A US5817827 A US 5817827A
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- US
- United States
- Prior art keywords
- amide
- amine
- sulphur trioxide
- triethylamine
- dehydration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/20—Preparation of carboxylic acid nitriles by dehydration of carboxylic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Definitions
- the present invention is concerned with a novel process for the manufacture of nitrites by dehydrating the corresponding amides.
- the object of the present invention is to provide a process for the manufacture of nitrites from amides by dehydration, in accordance with which the nitrile is obtained in a short reaction time, under mild reaction conditions and in high yield.
- the process in accordance with the invention comprises carrying out the dehydration in the presence of an adduct of sulphur trioxide and an amine in a basic reaction medium.
- the amine of this adduct is especially a tertiary amine.
- Aliphatic amines as well as nitrogen-containing heteroaromatic compounds are suitable amines for the formation of the sulphur trioxide-amine adduct.
- trialkylamines with straight-chain or branched alkyl residues containing 1 to 20 carbon atoms.
- alkyl residues are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert.butyl, n-pentyl, n-hexyl and n-octyl.
- the alkyl residues can be the same or different. Examples of these trialkylamines--and at the same time preferred trialkylamines--are triethylamine and diisopropylethylamine, respectively.
- the nitrogen-containing heteroaromatic compounds are especially heterocycles containing at least one ring nitrogen atom.
- Pyridine and pyridine derivatives such as picoline and quinoline, are examples.
- Such nitrogen-containing heteroaromatic compounds can also be bonded to a polymeric carrier. Pyridine is the most preferred of these compounds.
- An example of pyridine bonded to a polymeric carrier is poly-(4-vinyl-pyridine); the adduct of which with sulphur trioxide is commercially available (Fluka Chemie AG, CH-9471 Buchs, Switzerland).
- the use of the sulphur trioxide-amine adduct as the dehydrating reagent in the process in accordance with the invention is advantageous by virtue of its simple production from the educts sulphur trioxide and amine as well as the easier handling compared with the aggressive sulphur trioxide when this is used alone.
- the adducts are in part known and in some cases are commercially available. They can be produced readily by introducing sulphur trioxide into the diluted amine, methylene chloride, for example, being used as the diluent.
- the amide is reacted with the dehydrating reagent conveniently at room temperature, i.e. at about 25° C., or at elevated temperatures up to about 120° C., preferably at temperatures of about 50° C. to about 100° C., particularly at temperatures of about 70° C. to about 90° C.
- the dehydration is carried out in a basic reaction medium.
- the same amines which are used for the formation of the dehydrating reagent can be used as the reaction medium.
- Dehydration with sulphur trioxide-triethylamine adduct in triethylamine has been found to be especially advantageous.
- a mixture of the amine with an organic solvent can be used as the reaction medium, with aliphatic or cyclic ethers, e.g. tert.butyl methyl ether or, respectively, tetrahydrofuran or dioxan, aliphatic nitriles, e.g. acetonitrile, or aromatic hydrocarbons, e.g. toluene, being especially suitable organic solvents.
- no organic solvent is used.
- the molar ratio of amide to dehydrating reagent is conveniently about 1:1 to about 1:10, preferably about 1:1 to about 1:4, especially about 1:1 to about 1:2.5.
- the working up in order to obtain the crude product can be carried out according to appropriate methods used in organic chemistry.
- the latter can, for example, be converted with hydrogen chloride into a hydrochloride, in which case the hydrogen chloride can be used as dilute hydrochloric acid (e.g. 25% hydrochloric acid), as concentrated hydrochloric acid or even as gaseous hydrogen chloride.
- the crude product can also be isolated by distillation.
- the process in accordance with the invention enables nitriles to be manufactured from amides under mild reaction conditions and in high yields. It is suitable not only for the dehydration of aliphatic amides, but also of aromatic and heteroaromatic amides.
- Straight-chain or branched alkylamides such as hexanamide, for example, can be used as aliphatic amides.
- 2-Naphthalenecarboxamide, benzamide and substituted benzamides, such as 4-chlorobenzamide or 3,5-difluorobenzamide, can for example be used as aromatic amides.
- Nicotinamide can for example be used as the heteroaromatic amide.
- the process is especially suitable for the manufacture of 5-cyano-4-lower alkyl-oxazoles, such as 5-cyano-4-methyl-oxazole, a valuable intermediate in the synthesis of pyridoxine (vitamin B 6 ).
- the reaction mixture cooled to 0° C. in an ice bath, was treated with 150 ml of methyl tertiary butyl ether.
- concentrated hydrochloric acid was added dropwise until the pH value reached 7.
- the resulting precipitate was filtered off and washed with 100 ml of methyl tertiary butyl ether.
- the phases of the filtrate were separated and the aqueous phase was extracted twice with 50 ml of methyl tertiary butyl ether each time.
- the combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, dried over anhydrous sodium sulphate and filtered. Finally, the filtrate was concentrated on a rotary evaporator at 40° C. and 500 mbar. Yield: 93% of theory, determined by gas chromatography.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
Abstract
The present invention relates to a process for the dehydration of amides to nitrites which comprises carrying out the dehydration in the presence of an adduct of sulphur trioxide and an amine as the dehydrating reagent in a basic reaction mixture. Thereby, for example, aliphatic, aromatic and heteroaromatic amides are dehydrated to the corresponding nitrites, such as 5-carbamoyl-4-methyl-oxazole to 5-cyano-4-methyl-oxazole, a valuable intermediate in the synthesis of pyridoxine.
Description
The present invention is concerned with a novel process for the manufacture of nitrites by dehydrating the corresponding amides.
Several processes for the manufacture of nitriles by dehydrating the corresponding amides have become known in the last few years. One of these known processes comprises, for example, carrying out the dehydration in the presence of phosphorus pentoxide T. Rinderspacher and B. Prijs, Helv. Chim. Acta, 43, 1522-1530 (1960)!. The disadvantage of this process is, however, the low yield of product caused by the carbonization which occurs very readily in this reaction.
The object of the present invention is to provide a process for the manufacture of nitrites from amides by dehydration, in accordance with which the nitrile is obtained in a short reaction time, under mild reaction conditions and in high yield.
The process in accordance with the invention comprises carrying out the dehydration in the presence of an adduct of sulphur trioxide and an amine in a basic reaction medium. The amine of this adduct is especially a tertiary amine.
Aliphatic amines as well as nitrogen-containing heteroaromatic compounds are suitable amines for the formation of the sulphur trioxide-amine adduct.
Among the aliphatic amines in the scope of the present invention there can be used especially trialkylamines with straight-chain or branched alkyl residues containing 1 to 20 carbon atoms. Examples of such alkyl residues are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert.butyl, n-pentyl, n-hexyl and n-octyl. In such trialkylamines the alkyl residues can be the same or different. Examples of these trialkylamines--and at the same time preferred trialkylamines--are triethylamine and diisopropylethylamine, respectively.
The nitrogen-containing heteroaromatic compounds are especially heterocycles containing at least one ring nitrogen atom. Pyridine and pyridine derivatives, such as picoline and quinoline, are examples. Such nitrogen-containing heteroaromatic compounds can also be bonded to a polymeric carrier. Pyridine is the most preferred of these compounds. An example of pyridine bonded to a polymeric carrier is poly-(4-vinyl-pyridine); the adduct of which with sulphur trioxide is commercially available (Fluka Chemie AG, CH-9471 Buchs, Switzerland).
The use of the sulphur trioxide-amine adduct as the dehydrating reagent in the process in accordance with the invention is advantageous by virtue of its simple production from the educts sulphur trioxide and amine as well as the easier handling compared with the aggressive sulphur trioxide when this is used alone. The adducts are in part known and in some cases are commercially available. They can be produced readily by introducing sulphur trioxide into the diluted amine, methylene chloride, for example, being used as the diluent.
For the dehydration, the amide is reacted with the dehydrating reagent conveniently at room temperature, i.e. at about 25° C., or at elevated temperatures up to about 120° C., preferably at temperatures of about 50° C. to about 100° C., particularly at temperatures of about 70° C. to about 90° C.
The dehydration is carried out in a basic reaction medium. The same amines which are used for the formation of the dehydrating reagent can be used as the reaction medium. Dehydration with sulphur trioxide-triethylamine adduct in triethylamine has been found to be especially advantageous. If desired, a mixture of the amine with an organic solvent can be used as the reaction medium, with aliphatic or cyclic ethers, e.g. tert.butyl methyl ether or, respectively, tetrahydrofuran or dioxan, aliphatic nitriles, e.g. acetonitrile, or aromatic hydrocarbons, e.g. toluene, being especially suitable organic solvents. Preferably, however, no organic solvent is used.
When a solid amide is reacted, then the amide is conveniently suspended in the basic reaction medium.
The molar ratio of amide to dehydrating reagent is conveniently about 1:1 to about 1:10, preferably about 1:1 to about 1:4, especially about 1:1 to about 1:2.5.
After completion of the reaction the working up in order to obtain the crude product can be carried out according to appropriate methods used in organic chemistry. For the separation of the amine, the latter can, for example, be converted with hydrogen chloride into a hydrochloride, in which case the hydrogen chloride can be used as dilute hydrochloric acid (e.g. 25% hydrochloric acid), as concentrated hydrochloric acid or even as gaseous hydrogen chloride. The crude product can also be isolated by distillation.
The process in accordance with the invention enables nitriles to be manufactured from amides under mild reaction conditions and in high yields. It is suitable not only for the dehydration of aliphatic amides, but also of aromatic and heteroaromatic amides.
Straight-chain or branched alkylamides such as hexanamide, for example, can be used as aliphatic amides.
2-Naphthalenecarboxamide, benzamide and substituted benzamides, such as 4-chlorobenzamide or 3,5-difluorobenzamide, can for example be used as aromatic amides.
Nicotinamide can for example be used as the heteroaromatic amide.
The process is especially suitable for the manufacture of 5-cyano-4-lower alkyl-oxazoles, such as 5-cyano-4-methyl-oxazole, a valuable intermediate in the synthesis of pyridoxine (vitamin B6).
The following Examples illustrate the process in accordance with the invention in more detail, but are not intended to represent any limitation.
A suspension of 200 mmol of 5-carbamoyl-4-methyl-oxazole and 500 mmol of triethylamine-sulphur trioxide in 200 ml of triethylamine was stirred at 89° C. for 6 hours.
For the working up, the reaction mixture, cooled to 0° C. in an ice bath, was treated with 150 ml of methyl tertiary butyl ether. For neutralization, concentrated hydrochloric acid was added dropwise until the pH value reached 7. The resulting precipitate was filtered off and washed with 100 ml of methyl tertiary butyl ether. The phases of the filtrate were separated and the aqueous phase was extracted twice with 50 ml of methyl tertiary butyl ether each time. The combined organic phases were washed once with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, dried over anhydrous sodium sulphate and filtered. Finally, the filtrate was concentrated on a rotary evaporator at 40° C. and 500 mbar. Yield: 93% of theory, determined by gas chromatography.
A suspension of 200 mmol of 5-carbamoyl-4-methyl-oxazole and 500 mmol of diisopropylethylamine-sulphur trioxide in 200 ml of triethylamine was stirred at 89° C. for 6 hours. The working up was effected as described under a). Yield: 92% of theory.
A suspension of 200 mmol of 5-carbamoyl-4-methyl-oxazole and 500 mmol of pyridine-sulphur trioxide in 200 ml of triethylamine was stirred at 89° C. for 6 hours. The working up was effected as described under a). Yield: 45% of theory.
A suspension of 50 mmol of n-hexanamide and 125 mmol of triethylamine-sulphur trioxide in 75 ml of triethylamine was stirred at 89° C. for 6 hours. The working up was effected as described under Example 1a). Yield: 86% of theory.
A suspension of 50 mmol of 4-chlorobenzamide and 125 mmol of triethylamine-sulphur trioxide in 75 ml of triethylamine was stirred at 89° C. for 6 hours. The working up was effected as described under Example 1a). Yield: 92% of theory.
A suspension of 10 mmol of 3,5-difluorobenzamide and 25 mmol of triethylamine-sulphur trioxide in 30 ml of triethylamine was stirred at 89° C. for 1 hour. The working up was effected as described under Example 1a). Yield: 85.7% of theory.
A suspension of 10 mmol of naphthalenecarboxamide and 25 mmol of triethylamine-sulphur trioxide in 30 ml of triethylamine was stirred at 89° C. for 2 hours. The working up was effected as described under Example 1a). Yield: 91% of theory.
A suspension of 10 mmol of nicotinamide and 25 mmol of triethylamine-sulphur trioxide in 30 ml of triethylamine was stirred at 89° C. for 2 hours. The working up was effected as described under Example 1a). Yield: 95% of theory.
A suspension of 10 mmol of 5-ethoxy-4-methyloxazole-2-carboxamide and 25 mmol of triethylamine-sulphur trioxide in 30 ml of triethylamine was stirred at 89° C. for 6 hours. The working up was effected as described under Example 1a). Yield: 76% of theory.
Claims (11)
1. A method for producing a nitrile which comprises dehydrating an amide with a sulfur trioxide-tertiary amine adduct in a basic reaction medium at a temperature of from about 25° C. to about 120° C. to obtain the nitrile.
2. The method of claim 1, wherein the molar ratio of the amide to the sulphur trioxide-amine adduct is from about 1:1 to about 1:10.
3. The method of claim 1, wherein the amide is selected from the group consisting of an aliphatic amide, an aromatic amide and a heteroaromatic amide.
4. The method of claim 2, wherein the temperature is from about 50° C. to about 100° C.
5. The method of claim 2, wherein the molar ratio is from about 1:1 to about 1:4.
6. The method of claim 4, wherein the amine is an aliphatic amine or a nitrogen-containing heteroaromatic compound.
7. The method of claim 4, wherein the amine is pyridine or a pyridine derivative.
8. The method of claim 4, wherein the amine is a trialkylamine wherein each alkyl residue contains from 1 to 20 carbon atoms.
9. The method of claim 4, wherein the temperature is from about 70° C. to about 90° C.
10. The method of claim 5, wherein the molar ratio is from about 1:1 to about 1:2.5.
11. The method of claim 3, wherein the amide is 5-carbamoyl-4-methyl-oxazole.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH329095 | 1995-11-21 | ||
| CH3290/95 | 1995-11-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US5817827A true US5817827A (en) | 1998-10-06 |
Family
ID=4252791
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US08/734,987 Expired - Fee Related US5817827A (en) | 1995-11-21 | 1996-10-22 | Method for the dehydration of amides to nitriles |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5817827A (en) |
| EP (1) | EP0775691B1 (en) |
| JP (1) | JP3964485B2 (en) |
| CN (1) | CN1071311C (en) |
| AT (1) | ATE189209T1 (en) |
| DE (1) | DE59604290D1 (en) |
| DK (1) | DK0775691T3 (en) |
| ES (1) | ES2143126T3 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5965764A (en) * | 1997-08-06 | 1999-10-12 | Toray Industries, Inc. | Process for producing a nitrile |
| US20040028823A1 (en) * | 2002-08-08 | 2004-02-12 | Wilfried Dutt | Multi-layer coating process to achieve a highly saturated color appearance on a vehicle |
| WO2010018392A2 (en) | 2008-08-13 | 2010-02-18 | Hexcel Composites Limited | Novel curing agents and process for their manufacture |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102285902A (en) * | 2010-06-17 | 2011-12-21 | 刘�文 | Chlorination process method for production tower of para-cyanobenzyl chloride (ortho-cyanobenzyl chloride) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2783264A (en) * | 1955-03-21 | 1957-02-26 | American Cyanamid Co | Preparation of nitriles from amides |
| US4908452A (en) * | 1987-12-21 | 1990-03-13 | Merck & Co., Inc. | Process for preparing nitriles |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU891650A1 (en) * | 1978-09-11 | 1981-12-23 | Горьковский Политехнический Институт Им. А.А.Жданова | Method of preparing carboxylic acid nitriles |
-
1996
- 1996-10-22 US US08/734,987 patent/US5817827A/en not_active Expired - Fee Related
- 1996-10-25 JP JP28370096A patent/JP3964485B2/en not_active Expired - Fee Related
- 1996-11-13 CN CN96114461A patent/CN1071311C/en not_active Expired - Fee Related
- 1996-11-14 ES ES96118232T patent/ES2143126T3/en not_active Expired - Lifetime
- 1996-11-14 EP EP96118232A patent/EP0775691B1/en not_active Expired - Lifetime
- 1996-11-14 AT AT96118232T patent/ATE189209T1/en not_active IP Right Cessation
- 1996-11-14 DK DK96118232T patent/DK0775691T3/en active
- 1996-11-14 DE DE59604290T patent/DE59604290D1/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2783264A (en) * | 1955-03-21 | 1957-02-26 | American Cyanamid Co | Preparation of nitriles from amides |
| US4908452A (en) * | 1987-12-21 | 1990-03-13 | Merck & Co., Inc. | Process for preparing nitriles |
Non-Patent Citations (4)
| Title |
|---|
| Chemical Abstracts, vol. 86, No. 1, Jan. 3, 1977. * |
| Soviet Inventions Illustrated, Section Ch, Week 8243, Dec. 8, 1982. * |
| T. Rinderspacher and B. Prijs, Helv. Chim. Acta, 43, 1960, pp. 1522 1530. * |
| T. Rinderspacher and B. Prijs, Helv. Chim. Acta, 43, 1960, pp. 1522-1530. |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5965764A (en) * | 1997-08-06 | 1999-10-12 | Toray Industries, Inc. | Process for producing a nitrile |
| US20040028823A1 (en) * | 2002-08-08 | 2004-02-12 | Wilfried Dutt | Multi-layer coating process to achieve a highly saturated color appearance on a vehicle |
| WO2010018392A2 (en) | 2008-08-13 | 2010-02-18 | Hexcel Composites Limited | Novel curing agents and process for their manufacture |
Also Published As
| Publication number | Publication date |
|---|---|
| DK0775691T3 (en) | 2000-05-08 |
| DE59604290D1 (en) | 2000-03-02 |
| ES2143126T3 (en) | 2000-05-01 |
| EP0775691A1 (en) | 1997-05-28 |
| CN1071311C (en) | 2001-09-19 |
| CN1156721A (en) | 1997-08-13 |
| JP3964485B2 (en) | 2007-08-22 |
| JPH09169714A (en) | 1997-06-30 |
| ATE189209T1 (en) | 2000-02-15 |
| EP0775691B1 (en) | 2000-01-26 |
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